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Martino, M.;  Naso, V.;  Loteta, B.;  Canale, F.A.;  Pugliese, M.;  Alati, C.;  Musuraca, G.;  Nappi, D.;  Gaimari, A.;  Nicolini, F.; et al. Chimeric Antigen Receptor T-Cell Therapy. Encyclopedia. Available online: https://encyclopedia.pub/entry/35853 (accessed on 13 October 2024).
Martino M,  Naso V,  Loteta B,  Canale FA,  Pugliese M,  Alati C, et al. Chimeric Antigen Receptor T-Cell Therapy. Encyclopedia. Available at: https://encyclopedia.pub/entry/35853. Accessed October 13, 2024.
Martino, Massimo, Virginia Naso, Barbara Loteta, Filippo Antonio Canale, Marta Pugliese, Caterina Alati, Gerardo Musuraca, Davide Nappi, Anna Gaimari, Fabio Nicolini, et al. "Chimeric Antigen Receptor T-Cell Therapy" Encyclopedia, https://encyclopedia.pub/entry/35853 (accessed October 13, 2024).
Martino, M.,  Naso, V.,  Loteta, B.,  Canale, F.A.,  Pugliese, M.,  Alati, C.,  Musuraca, G.,  Nappi, D.,  Gaimari, A.,  Nicolini, F.,  Mazza, M.,  Bravaccini, S.,  Derudas, D.,  Martinelli, G., & Cerchione, C. (2022, November 22). Chimeric Antigen Receptor T-Cell Therapy. In Encyclopedia. https://encyclopedia.pub/entry/35853
Martino, Massimo, et al. "Chimeric Antigen Receptor T-Cell Therapy." Encyclopedia. Web. 22 November, 2022.
Chimeric Antigen Receptor T-Cell Therapy
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The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective CAR-T. Chimeric antigen receptor T-cell therapy (CAR-T) is a type of immunotherapy in which a patient’s T cells are collected and genetically engineered to improve their ability to recognize and kill cancer cells. However, several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable.

CAR-T manufacturing toxicities

1. Introduction

Chimeric antigen receptor T-cell therapy (CAR-T) is a type of immunotherapy in which a patient’s T cells, immune cells with anti-cancer activity, are collected and genetically engineered to improve their tropism and promote the elimination of cancer cells [1][2][3][4]. The modified cells are expanded in the laboratory and then returned to the patient to fight cancer. The year 2018 represents a milestone in the history of medicine: the Food and Drug Administration (FDA) [5][6] and the European Medicines Agency (EMA) [7] approved the first two products containing autologous T cells genetically modified ex vivo, tisagenlecleucel and axicabtageneciloleucel, for commercial use, revolutionizing the treatment landscape for relapsed or refractory (R/R) ALL and R/R non-Hodgkin lymphoma (NHL). However, history goes on, and in the last year, the FDA approved lisocabtagenemaraleucel in R/R NHL [8] and idecabtagenevicleucel in R/R multiple myeloma (MM) [9][10][11]. In addition, brexucabtageneautoleucel has been approved for treating adult patients with R/R mantle cell lymphoma [12] and is now being studied in patients with R/R B-ALL [13]. Moreover, the rolling submission of a biologics license application has been completed to support the approval of the investigational ciltacabtageneautoleucel in R/R MM [14]. Researchers also published data about an autologous CAR-T that uses a novel binding domain to target a B-cell maturation antigen (CARTddBCMA) in R/R MM, designed to reduce the risk of immunogenicity, while increasing stability [15]. The main characteristics of the constructs and the clinical indications are summarized in Table 1.
Table 1. Main characteristics of the CAR-T constructs and clinical indications.

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